Two newly developed experimental systems of organ-specific autoimmune disease will be used to study the age-related changes in T cell regulation of murine autoimmunity. One method is based on induction of autoimmune disease in selected strains of mice by neonatal thymectomy (NTx). In the other method, athymic nude mice are reconstituted with particular T cell subsets from spleens of H-2 matched euthymic mice. Thyroiditis, gastritis with macrocytic anemia, and oophoritis are produced by both methods, depending upon the strain of mice used. In both experimental systems, regulatory T cell subsets seem to play a primary role in maintaining self-non-self discrimination.